Annals of Biomedical Engineering

, Volume 34, Issue 1, pp 102–113 | Cite as

Nanoscale Intracellular Organization and Functional Architecture Mediating Cellular Behavior

  • Philip P. LeDucEmail author
  • Robert R. Bellin


Cells function based on a complex set of interactions that control pathways resulting in ultimate cell fates including proliferation, differentiation, and apoptosis. The interworkings of this immensely dense network of intracellular molecules are influenced by more than random protein and nucleic acid distribution where their interactions culminate in distinct cellular function. By probing the design of these biological systems from an engineering perspective, researchers can gain great insight that will aid in building and utilizing systems that are on this size scale where traditional large-scale rules may fail to apply. The organized interaction and gradient distribution in intracellular space imply a structural architecture that modulates cellular processes by influencing biochemical interactions including transport and binding-reactions. One significant structure that plays a role in this modulation is the cell cytoskeleton. Here, we discuss the cytoskeleton as a central and integrating functional structure in influencing cell processes and we describe technology useful for probing this structure. We explain the nanometer scale science of cytoskeletal structure with respect to intracellular organization, mechanotransduction, cytoskeletal-associated proteins, and motor molecules, as well as nano- and microtechnologies that are applicable for experimental studies of the cytoskeleton. This biological architecture of the cytoskeleton influences molecular, cellular, and physiological processes through structured multimodular and hierarchical principles centered on these functional filaments. Through investigating these organic systems that have evolved over billions of years, understanding in biology, engineering, and nanometer-scaled science will be advanced.


Cytoskeleton Nanotechnology Nanoscience Intracellular organization Structure 



This work was supported in part by grants from the National Science Foundation (R.B.), National Science Foundation-CAREER (P.L.), Pennsylvania Infrastructure Technology Alliance, and the Department of Energy-Genome to Life Program. The authors would also like to thank M. L. Ledbetter, S. LeDuc, S. Lawrence, and W. Messner for their helpful discussions and input on the manuscript.


  1. 1.
    Alenghat, F. J., B. Fabry, K. Y. Tsai, W. H. Goldmann, and D. E. Ingber. Analysis of cell mechanics in single vinculin-deficient cells using a magnetic tweezer. Biochem. Biophys. Res. Commun. 277:93–99, 2000.CrossRefPubMedGoogle Scholar
  2. 2.
    Alenghat, F. J., and D. E. Ingber. Mechanotransduction: All signals point to cytoskeleton, matrix, and integrins. Sci. STKE 119:PE6, 2002.Google Scholar
  3. 3.
    Baluska, F., and P. W. Barlow. The role of the microtubular cytoskeleton in determining nuclear chromatin structure and passage of maize root cells through the cell cycle. Eur. J. Cell Biol. 61:160–167, 1993.PubMedGoogle Scholar
  4. 4.
    Beato, M., M. Truss, and S. Chavez. Control of transcription by steroid hormones. Ann. N. Y. Acad. Sci. 784:93–123, 1996.PubMedGoogle Scholar
  5. 5.
    Bellin, R. M., T. W. Huiatt, D. R. Critchley, and R. M. Robson. Synemin may function to directly link muscle cell intermediate filaments to both myofibrillar z-lines and costameres. J. Biol. Chem. 276:32330–32337, 2001.CrossRefPubMedGoogle Scholar
  6. 6.
    Benjamin, M., C. W. Archer, and J. R. Ralphs. Cytoskeleton of cartilage cells. Microsc. Res. Tech. 28:372–377, 1994.CrossRefPubMedGoogle Scholar
  7. 7.
    Bogre, L., O. Calderini, I. Merskiene, and P. Binarova. Regulation of cell division and the cytoskeleton by mitogen-activated protein kinases in higher plants. Results Probl. Cell Differ. 27:95–117, 2000.PubMedGoogle Scholar
  8. 8.
    Casanova, J. E. Epithelial cell cytoskeleton and intracellular trafficking v. Confluence of membrane trafficking and motility in epithelial cell models. Am. J. Physiol. Gastrointest. Liver Physiol. 283:G1015–G1019, 2002.PubMedGoogle Scholar
  9. 9.
    Chen, C. S., M. Mrksich, S. Huang, G. M. Whitesides, and D. E. Ingber. Geometric control of cell life and death. Science 276:1425–1428, 1997.CrossRefPubMedGoogle Scholar
  10. 10.
    Chicurel, M. E., R. H. Singer, C. J. Meyer, and D. E. Ingber. Integrin binding and mechanical tension induce movement of mRNA and ribosomes to focal adhesions. Nature 392:730–733, 1998.CrossRefPubMedGoogle Scholar
  11. 11.
    Cole, N. B., C. L. Smith, N. Sciaky, M. Terasaki, M. Edidin, and J. Lippincott-Schwartz. Diffusional mobility of golgi proteins in membranes of living cells. Science 273:797–801, 1996.PubMedGoogle Scholar
  12. 12.
    Costa, K. D., W. J. Hucker, and F. C. Yin. Buckling of actin stress fibers: A new wrinkle in the cytoskeletal tapestry. Cell Motil. Cytoskeleton 52:266–274, 2002.CrossRefPubMedGoogle Scholar
  13. 13.
    Csermely, P. A nonconventional role of molecular chaperones: Involvement in the cytoarchitecture. News Physiol. Sci. 16:123–126, 2001.PubMedGoogle Scholar
  14. 14.
    Csermely, P., T. Schnaider, C. Soti, Z. Prohaszka, and G. Nardai. The 90-kda molecular chaperone family: Structure, function, and clinical applications. A comprehensive review. Pharmacol. Ther. 79:129–168, 1998.CrossRefPubMedGoogle Scholar
  15. 15.
    Dalby, M. J., S. J. Yarwood, M. O. Riehle, H. J. Johnstone, S. Affrossman, and A. S. Curtis. Increasing fibroblast response to materials using nanotopography: Morphological and genetic measurements of cell response to 13-nm-high polymer demixed islands. Exp. Cell Res. 276:1–9, 2002.CrossRefPubMedGoogle Scholar
  16. 16.
    de Castro, R. D., A. A. van Lammeren, S. P. Groot, R. J. Bino, and H. W. Hilhorst. Cell division and subsequent radicle protrusion in tomato seeds are inhibited by osmotic stress but DNA synthesis and formation of microtubular cytoskeleton are not. Plant Physiol. 122:327–336, 2000.CrossRefPubMedGoogle Scholar
  17. 17.
    Dekker, R. J., S. van Soest, R. D. Fontijn, S. Salamanca, P. G. de Groot, E. VanBavel, H. Pannekoek, and A. J. Horrevoet. Prolonged fluid shear stress induces a distinct set of endothelial cell genes, most specifically lung kruppel-like factor (klf2). Blood 100:1689–1698, 2002.CrossRefPubMedGoogle Scholar
  18. 18.
    Desai, T. A. Microfabrication technology for pancreatic cell encapsulation. Expert Opin. Biol. Ther. 2:633–646, 2002.CrossRefPubMedGoogle Scholar
  19. 19.
    Engstrom, K. G., and H. J. Meiselman. Combined use of micropipette aspiration and perifusion for studying red blood cell volume regulation. Cytometry 27:345–352, 1997.CrossRefPubMedGoogle Scholar
  20. 20.
    Farinas, J., A. W. Chow, and H. G. Wada. A microfluidic device for measuring cellular membrane potential. Anal. Biochem. 295:138–142, 2001.CrossRefPubMedGoogle Scholar
  21. 21.
    Fath, K. R., S. N. Mamajiwalla, and D. R. Burgess. The cytoskeleton in development of epithelial cell polarity. J. Cell Sci. 17 (Suppl.):65–73, 1993.Google Scholar
  22. 22.
    Ferrer, I., R. Blanco, M. Carmona, B. Puig, M. Barrachina, C. Gomez, and S. Ambrosio. Active, phosphorylation-dependent mitogen-activated protein kinase (mapk/erk), stress-activated protein kinase/c-jun n-terminal kinase (sapk/jnk), and p38 kinase expression in parkinson's disease and dementia with lewy bodies. J. Neural Transm. 108:1383–1396, 2001.CrossRefPubMedGoogle Scholar
  23. 23.
    Fleming, T. P., P. M. Cannon, and S. J. Pickering. The cytoskeleton, endocytosis and cell polarity in the mouse preimplantation embryo. Dev. Biol. 113:406–419, 1986.CrossRefPubMedGoogle Scholar
  24. 24.
    Fluck, M., J. A. Carson, S. E. Gordon, A. Ziemiecki, and F. W. Booth. Focal adhesion proteins fak and paxillin increase in hypertrophied skeletal muscle. Am. J. Physiol. 277:C152–C162, 1999.PubMedGoogle Scholar
  25. 25.
    Folch, A., and M. Toner. Cellular micropatterns on biocompatible materials. Biotechnol. Prog. 14:388–392, 1998.CrossRefPubMedGoogle Scholar
  26. 26.
    Fox, J. A., T. E. Hotaling, C. Struble, J. Ruppel, D. J. Bates, and M. B. Schoenhoff. Tissue distribution and complex formation with ige of an anti-ige antibody after intravenous administration in cynomolgus monkeys. J. Pharmacol. Exp. Ther. 279:1000–1008, 1996.PubMedGoogle Scholar
  27. 27.
    Freitas, R. A. Jr. Exploratory design in medical nanotechnology: A mechanical artificial red cell. Artif. Cells Blood Substit. Immobil. Biotechnol. 26:411–430, 1998.PubMedCrossRefGoogle Scholar
  28. 28.
    Fu, A. Y., H. P. Chou, C. Spence, F. H. Arnold, and S. R. Quake. An integrated microfabricated cell sorter. Anal. Chem. 74:2451–2457, 2002.CrossRefPubMedGoogle Scholar
  29. 29.
    Galigniana, M. D., J. L. Scruggs, J. Herrington, M. J. Welsh, C. Carter-Su, P. R. Housley, and W. B. Pratt. Heat shock protein 90-dependent (geldanamycin-inhibited) movement of the glucocorticoid receptor through the cytoplasm to the nucleus requires intact cytoskeleton. Mol. Endocrinol. 12:1903–1913, 1998.CrossRefPubMedGoogle Scholar
  30. 30.
    Gao, X., Y. Cui, R. M. Levenson, L. W. Chung, and S. Nie. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat. Biotechnol. 22:969–976, 2004.CrossRefPubMedGoogle Scholar
  31. 31.
    Garcia-Cardena, G., J. I. Comander, B. R. Blackman, K. R. Anderson, and M. A. Gimbrone. Mechanosensitive endothelial gene expression profiles: Scripts for the role of hemodynamics in atherogenesis? Ann. N. Y. Acad. Sci. 947:1–6, 2001.PubMedCrossRefGoogle Scholar
  32. 32.
    Hable, W. E., and D. L. Kropf. Roles of secretion and the cytoskeleton in cell adhesion and polarity establishment in pelvetia compressa zygotes. Dev. Biol. 198:45–56, 1998.PubMedGoogle Scholar
  33. 33.
    Hasezawa, S., and F. Kumagai. Dynamic changes and the role of the cytoskeleton during the cell cycle in higher plant cells. Int. Rev. Cytol. 214:161–191, 2002.PubMedGoogle Scholar
  34. 34.
    Helmke, B. P., and P. F. Davies. The cytoskeleton under external fluid mechanical forces: Hemodynamic forces acting on the endothelium. Ann. Biomed. Eng. 30:284–296, 2002.CrossRefPubMedGoogle Scholar
  35. 35.
    Helmke, B. P., A. B. Rosen, and P. F. Davies. Mapping mechanical strain of an endogenous cytoskeletal network in living endothelial cells. Biophys. J. 84:2691–2699, 2003.PubMedGoogle Scholar
  36. 36.
    Holth, L. T., D. N. Chadee, V. A. Spencer, S. K. Samuel, J. R. Safneck, and J. R. Davie. Chromatin, nuclear matrix and the cytoskeleton: Role of cell structure in neoplastic transformation (review). Int. J. Oncol. 13:827–837, 1998.PubMedGoogle Scholar
  37. 37.
    Htun, H., J. Barsony, I. Renyi, D. L. Gould, and G. L. Hager. Visualization of glucocorticoid receptor translocation and intranuclear organization in living cells with a green fluorescent protein chimera. Proc. Natl. Acad. Sci. U.S.A. 93:4845–4850, 1996.CrossRefPubMedGoogle Scholar
  38. 38.
    Htun, H., L. T. Holth, D. Walker, J. R. Davie, and G. L. Hager. Direct visualization of the human estrogen receptor alpha reveals a role for ligand in the nuclear distribution of the receptor. Mol. Biol. Cell 10:471–486, 1999.PubMedGoogle Scholar
  39. 39.
    Hu, S., J. Chen, B. Fabry, Y. Numaguchi, A. Gouldstone, D. E. Ingber, J. J. Fredberg, J. P. Butler, and N. Wang. Intracellular stress tomography reveals stress focusing and structural anisotropy in cytoskeleton of living cells. Am. J. Physiol. Cell Physiol. 285:C1082–C1090, 2003PubMedGoogle Scholar
  40. 40.
    Hu, J., Z. H. Wang, and Z. L. Tao. Micropatterning of biotin-avidin layers and cell location. Sheng Wu Gong Cheng Xue Bao 18:619–621, 2002.PubMedGoogle Scholar
  41. 41.
    Huang, S., and D. E. Ingber. A discrete cell cycle checkpoint in late g(1) that is cytoskeleton-dependent and map kinase (erk)-independent. Exp. Cell Res. 275:255–264, 2002.CrossRefPubMedGoogle Scholar
  42. 42.
    Huang, Y., E. L. Mather, J. L. Bell, and M. Madou. Mems-based sample preparation for molecular diagnostics. Anal. Bioanal. Chem. 372:49–65, 2002.CrossRefPubMedGoogle Scholar
  43. 43.
    Huen, A. C., J. K. Park, L. M. Godsel, X. Chen, L. J. Bannon, E. V. Amarg, T. Y. Hudson, A. K. Mongiu, I. M. Leigh, D. Kelsell, B. M. Gumbiner, and K. J. Green. Intermediate filament-membrane attachments function synergistically with actin-dependent contacts to regulate intercellular adhesive strength. J. Cell Biol. 159:1005–1017, 2002.CrossRefPubMedGoogle Scholar
  44. 44.
    Hutcheson, I. R., and T. M. Griffith. Mechanotransduction through the endothelial cytoskeleton: Mediation of flow- but not agonist-induced edrf release. Br. J. Pharmacol. 118:720–726, 1996.PubMedGoogle Scholar
  45. 45.
    Ishikawa, H. Cell polarity and cytoskeleton. Tanpakushitsu Kakusan Koso 34:1742–1748, 1989.PubMedGoogle Scholar
  46. 46.
    Izutsu, K. Cell division and the microtubular cytoskeleton. Hum. Cell 4:100–108, 1991.PubMedGoogle Scholar
  47. 47.
    Kaibuchi, K., S. Kuroda, and M. Amano. Regulation of the cytoskeleton and cell adhesion by the rho family gtpases in mammalian cells. Annu. Rev. Biochem. 68:459–486, 1999.CrossRefPubMedGoogle Scholar
  48. 48.
    Kane, R. S., S. Takayama, E. Ostuni, D. E. Ingber, and G. M. Whitesides. Patterning proteins and cells using soft lithography. Biomaterials 20:2363–2376, 1999.CrossRefPubMedGoogle Scholar
  49. 49.
    Kano, Y., K. Katoh, and K. Fujiwara. Lateral zone of cell–cell adhesion as the major fluid shear stress-related signal transduction site. Circ. Res. 86:425–433, 2000.PubMedGoogle Scholar
  50. 50.
    Kataoka, N., K. Iwaki, K. Hashimoto, S. Mochizuki, Y. Ogasawara, M. Sato, K. Tsujioka, and F. Kajiya. Measurements of endothelial cell-to-cell and cell-to-substrate gaps and micromechanical properties of endothelial cells during monocyte adhesion. Proc. Natl. Acad. Sci. U.S.A. 99:15638–15643, 2002.CrossRefPubMedGoogle Scholar
  51. 51.
    Kenis, P. J., R. F. Ismagilov, and G. M. Whitesides. Microfabrication inside capillaries using multiphase laminar flow patterning. Science 285:83–85, 1999.CrossRefPubMedGoogle Scholar
  52. 52.
    Kubicek, J. D., S. Brelsford, P. Ahluwalia, and P. R. Leduc. Integrated lithographic membranes and surface adhesion chemistry for three-dimensional cellular stimulation. Langmuir 20:11552–11556, 2004.CrossRefPubMedGoogle Scholar
  53. 53.
    Kural, C., H. Kim, S. Syed, G. Goshima, V. I. Gelfand, and P. R. Selvin. Kinesin and dynein move a peroxisome in vivo: A tug-of-war or coordinated movement? Science 308:1469–1472, 2005.CrossRefPubMedGoogle Scholar
  54. 54.
    LeDuc, P., C. Haber, G. Bao, and D. Wirtz. Dynamics of individual flexible polymers in a shear flow. Nature 399:564–566, 1999.CrossRefPubMedGoogle Scholar
  55. 55.
    LeDuc, P., E. Ostuni, G. Whitesides, and D. Ingber. Use of micropatterned adhesive surfaces for control of cell behavior. Methods Cell Biol. 69:385–401, 2002.CrossRefPubMedGoogle Scholar
  56. 56.
    Li, C., Y. Hu, M. Mayr, and Q. Xu. Cyclic strain stress-induced mitogen-activated protein kinase (mapk) phosphatase 1 expression in vascular smooth muscle cells is regulated by ras/rac-mapk pathways. J. Biol. Chem. 274:25273–25280, 1999.CrossRefPubMedGoogle Scholar
  57. 57.
    Li, Y. Q., A. Moscatelli, G. Cai, and M. Cresti. Functional interactions among cytoskeleton, membranes, and cell wall in the pollen tube of flowering plants. Int. Rev. Cytol. 176:133–199, 1997.PubMedCrossRefGoogle Scholar
  58. 58.
    Li Jeon, N., H. Baskaran, S. K. Dertinger, G. M. Whitesides, L. van de Water, and M. Toner. Neutrophil chemotaxis in linear and complex gradients of interleukin-8 formed in a microfabricated device. Nat. Biotechnol. 20:826–830, 2002.PubMedGoogle Scholar
  59. 59.
    Liu, J., Q. Zhang, E. E. Remsen, and K. L. Wooley. Nanostructured materials designed for cell binding and transduction. Biomacromolecules 2:362–368, 2001.CrossRefPubMedGoogle Scholar
  60. 60.
    Machesky, L. M., and J. A. Cooper. Cell motility. Bare bones of the cytoskeleton. Nature 401:542–543, 1999.CrossRefPubMedGoogle Scholar
  61. 61.
    Malek, A. M., and S. Izumo. Mechanism of endothelial cell shape change and cytoskeletal remodeling in response to fluid shear stress. J. Cell Sci. 109(Pt 4):713–726, 1996.PubMedGoogle Scholar
  62. 62.
    Maniotis, A. J., K. Bojanowski, and D. E. Ingber. Mechanical continuity and reversible chromosome disassembly within intact genomes removed from living cells. J. Cell. Biochem. 65:114–130, 1997.CrossRefPubMedGoogle Scholar
  63. 63.
    Maniotis, A. J., C. S. Chen, and D. E. Ingber. Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc. Natl. Acad. Sci. U.S.A. 94:849–854, 1997.CrossRefPubMedGoogle Scholar
  64. 64.
    Matsuda, T., K. Inoue, and T. Sugawara. Development of micropatterning technology for cultured cells. ASAIO Trans. 36:M559–M562, 1990.PubMedGoogle Scholar
  65. 65.
    Meyer, C. J., F. J. Alenghat, P. Rim, J. H. Fong, B. Fabry, and D. E. Ingber. Mechanical control of cyclic amp signalling and gene transcription through integrins. Nat. Cell Biol. 2:666–668, 2000.CrossRefPubMedGoogle Scholar
  66. 66.
    Miller, C., S. Jeftinija, and S. Mallapragada. Micropatterned schwann cell-seeded biodegradable polymer substrates significantly enhance neurite alignment and outgrowth. Tissue Eng. 7:705–715, 2001.CrossRefPubMedGoogle Scholar
  67. 67.
    Miller, C., H. Shanks, A. Witt, G. Rutkowski, and S. Mallapragada. Oriented schwann cell growth on micropatterned biodegradable polymer substrates. Biomaterials 22:1263–1269, 2001.CrossRefPubMedGoogle Scholar
  68. 68.
    Minton, A. P. Implications of macromolecular crowding for protein assembly. Curr. Opin. Struct. Biol. 10:34–39, 2000.CrossRefPubMedGoogle Scholar
  69. 69.
    Minton, A. P. The influence of macromolecular crowding and macromolecular confinement on biochemical reactions in physiological media. J. Biol. Chem. 276:10577–10580, 2001.CrossRefPubMedGoogle Scholar
  70. 70.
    Moon, J. J., M. Matsumoto, S. Patel, L. Lee, J. L. Guan, and S. Li. Role of cell surface heparan sulfate proteoglycans in endothelial cell migration and mechanotransduction. J. Cell. Physiol. 203:166–176, 2004.CrossRefGoogle Scholar
  71. 71.
    Morimoto, N., R. M. Raphael, A. Nygren, and W. E. Brownell. Excess plasma membrane and effects of ionic amphipaths on mechanics of outer hair cell lateral wall. Am. J. Physiol. Cell Physiol. 282:C1076–C1086, 2002.PubMedGoogle Scholar
  72. 72.
    Nelson, W. J., R. W. Hammerton, A. Z. Wang, and E. M. Shore. Involvement of the membrane-cytoskeleton in development of epithelial cell polarity. Semin. Cell Biol. 1:359–371, 1990.PubMedGoogle Scholar
  73. 73.
    Ogawa, H., S. Inouye, F. I. Tsuji, K. Yasuda, and K. Umesono. Localization, trafficking, and temperature-dependence of the aequorea green fluorescent protein in cultured vertebrate cells. Proc. Natl. Acad. Sci. U.S.A. 92:11899–11903, 1995.PubMedGoogle Scholar
  74. 74.
    Parry, G., J. C. Beck, L. Moss, J. Bartley, and G. K. Ojakian. Determination of apical membrane polarity in mammary epithelial cell cultures: The role of cell–cell, cell–substratum, and membrane–cytoskeleton interactions. Exp. Cell Res. 188:302–311, 1990.CrossRefPubMedGoogle Scholar
  75. 75.
    Patel, N., R. Bhandari, K. M. Shakesheff, S. M. Cannizzaro, M. C. Davies, R. Langer, C. J. Roberts, S. J. Tendler, and P. M. Williams. Printing patterns of biospecifically-adsorbed protein. J. Biomater. Sci. Polym. Ed. 11:319–331, 2000.CrossRefPubMedGoogle Scholar
  76. 76.
    Plopper, G., and D. E. Ingber. Rapid induction and isolation of focal adhesion complexes. Biochem. Biophys. Res. Commun. 193:571–578, 1993.CrossRefPubMedGoogle Scholar
  77. 77.
    Pollack, G. Cells, Gels, and the Engines of Life. Seattle, WA: Ebner, 2001Google Scholar
  78. 78.
    Prima, V., C. Depoix, B. Masselot, P. Formstecher, and P. Lefebvre. Alteration of the glucocorticoid receptor subcellular localization by non steroidal compounds. J. Steroid Biochem. Mol. Biol. 72:1–12, 2000.CrossRefPubMedGoogle Scholar
  79. 79.
    Puskar, K., L. Apelstein, S. Ta'asan, R. Schwartz, and P. LeDuc. Understanding actin organization in cell structure through lattice based monte carlo simulations. MCB 1:123–132, 2004.PubMedGoogle Scholar
  80. 80.
    Quake, S. R., and A. Scherer. From micro- to nanofabrication with soft materials. Science 290:1536–1540, 2000.CrossRefPubMedGoogle Scholar
  81. 81.
    Reipert, S., F. Steinbock, I. Fischer, R. E. Bittner, A. Zeold, and G. Wiche. Association of mitochondria with plectin and desmin intermediate filaments in striated muscle. Exp. Cell Res. 252:479–491, 1999.CrossRefPubMedGoogle Scholar
  82. 82.
    Resnick, N., H. Yahav, L. M. Khachigian, T. Collins, K. R. Anderson, F. C. Dewey, and M. A. Gimbrone. Endothelial gene regulation by laminar shear stress. Adv. Exp. Med. Biol. 430:155–164, 1997.PubMedGoogle Scholar
  83. 83.
    Rivas, G., J. A. Fernandez, and A. P. Minton. Direct observation of the enhancement of noncooperative protein self-assembly by macromolecular crowding: Indefinite linear self-association of bacterial cell division protein ftsz. Proc. Natl. Acad. Sci. U.S.A. 98:3150–3155, 2001.CrossRefPubMedGoogle Scholar
  84. 84.
    Rivero, F., B. Koppel, B. Peracino, S. Bozzaro, F. Siegert, C. J. Weijer, M. Schleicher, R. Albrecht, and A. A. Noegel. The role of the cortical cytoskeleton: F-actin crosslinking proteins protect against osmotic stress, ensure cell size, cell shape and motility, and contribute to phagocytosis and development. J. Cell Sci. 109(Pt 11):2679–2691, 1996.PubMedGoogle Scholar
  85. 85.
    Salter, D. M., S. J. Millward-Sadler, G. Nuki, and M. O. Wright. Integrin-interleukin-4 mechanotransduction pathways in human chondrocytes. Clin. Orthop. S49–S60, 2001.Google Scholar
  86. 86.
    Sanger, J. W., and J. M. Sanger. The cytoskeleton and cell division. Methods Achiev. Exp. Pathol. 8:110–142, 1979.PubMedGoogle Scholar
  87. 87.
    Schnittler, H. J., S. W. Schneider, H. Raifer, F. Luo, P. Dieterich, I. Just, and K. Aktories. Role of actin filaments in endothelial cell–cell adhesion and membrane stability under fluid shear stress. Pflugers Arch. 442:675–687, 2001.CrossRefPubMedGoogle Scholar
  88. 88.
    Shafrir, Y., and G. Forgacs. Mechanotransduction through the cytoskeleton. Am. J. Physiol. Cell Physiol. 282:C479–C486, 2002.PubMedGoogle Scholar
  89. 89.
    Shen, N., D. Datta, C. B. Schaffer, P. LeDuc, D. E. Ingber, and E. Mazur. Ablation of cytoskeletal filaments and mitochondria in live cells using a femtosecond laser nanoscissor. Mech. Chem. Biosyst. 2:17–25, 2005.PubMedGoogle Scholar
  90. 90.
    Shrode, L. D., E. A. Rubie, J. R. Woodgett, and S. Grinstein. Cytosolic alkalinization increases stress-activated protein kinase/c-jun nh2-terminal kinase (sapk/jnk) activity and p38 mitogen-activated protein kinase activity by a calcium-independent mechanism. J. Biol. Chem. 272:13653–13659, 1997.CrossRefPubMedGoogle Scholar
  91. 91.
    Silverstein, R. L., L. L. Leung, P. C. Harpel, and R. L. Nachman. Complex formation of platelet thrombospondin with plasminogen. Modulation of activation by tissue activator. J. Clin. Invest. 74:1625–1633, 1984.PubMedGoogle Scholar
  92. 92.
    Singhvi, R., A. Kumar, G. P. Lopez, G. N. Stephanopoulos, D. I. Wang, G. M. Whitesides, and D. E. Ingber. Engineering cell shape and function. Science 264:696–698, 1994.PubMedGoogle Scholar
  93. 93.
    Small, J. V., and M. Gimona. The cytoskeleton of the vertebrate smooth muscle cell. Acta Physiol. Scand. 164:341–348, 1998.CrossRefPubMedGoogle Scholar
  94. 94.
    Small, J. V., I. Kaverina, O. Krylyshkina, and K. Rottner. Cytoskeleton cross-talk during cell motility. FEBS Lett. 452:96–99, 1999.CrossRefPubMedGoogle Scholar
  95. 95.
    Soll, D. R. Researchers in cell motility and the cytoskeleton can play major roles in understanding aids. Cell Motil. Cytoskeleton 37:91–97, 1997.CrossRefPubMedGoogle Scholar
  96. 96.
    Spector, A. A., M. Ameen, P. G. Charalambides, and A. S. Popel. Nanostructure, effective properties, and deformation pattern of the cochlear outer hair cell cytoskeleton. J. Biomech. Eng. 124:180–187, 2002.CrossRefPubMedGoogle Scholar
  97. 97.
    Steinbock, F. A., and G. Wiche. Plectin: A cytolinker by design. Biol. Chem. 380:151–158, 1999.CrossRefPubMedGoogle Scholar
  98. 98.
    Streiblova, E., and J. Hasek. Role of the cytoskeleton and homologs of retrovirus genes in yeast cell division. Izv. Akad. Nauk SSSR Biol. 353–360, 1987.Google Scholar
  99. 99.
    Svoboda, A., I. Slaninova, and A. Holubarova. Cytoskeleton in regenerating protoplasts and restoration of cell polarity in the yeast saccharomyces cerevisiae. Acta Biol. Hung. 52:325–333, 2001.CrossRefPubMedGoogle Scholar
  100. 100.
    Takayama, S., E. Ostuni, P. LeDuc, K. Naruse, D. E. Ingber, and G. M. Whitesides. Subcellular positioning of small molecules. Nature 411:1016, 2001.CrossRefPubMedGoogle Scholar
  101. 101.
    Takayama, S., E. Ostuni, P. LeDuc, K. Naruse, D. E. Ingber, and G. M. Whitesides. Selective chemical treatment of cellular microdomains using multiple laminar streams. Chem. Biol. 10:123–130, 2003.CrossRefPubMedGoogle Scholar
  102. 102.
    Terray, A., J. Oakey, and D. W. Marr. Microfluidic control using colloidal devices. Science 296:1841–1844, 2002.CrossRefPubMedGoogle Scholar
  103. 103.
    Thiebaud, P., L. Lauer, W. Knoll, and A. Offenhausser. Pdms device for patterned application of microfluids to neuronal cells arranged by microcontact printing. Biosens. Bioelectron. 17:87–93, 2002.CrossRefPubMedGoogle Scholar
  104. 104.
    Tien, J., C. M. Nelson, and C. S. Chen. Fabrication of aligned microstructures with a single elastomeric stamp. Proc. Natl. Acad. Sci. U.S.A. 99:1758–1762, 2002.CrossRefPubMedGoogle Scholar
  105. 105.
    Topper, J. N., and M. A. Gimbrone Jr. Blood flow and vascular gene expression: Fluid shear stress as a modulator of endothelial phenotype. Mol. Med. Today 5:40–46, 1999.CrossRefPubMedGoogle Scholar
  106. 106.
    Truskey, G. A., and J. S. Pirone. The effect of fluid shear stress upon cell adhesion to fibronectin-treated surfaces. J. Biomed. Mater. Res. 24:1333–1353, 1990.CrossRefPubMedGoogle Scholar
  107. 107.
    Tsai, M. J., and B. W. O'Malley. Molecular mechanisms of action of steroid/thyroid receptor superfamily members. Annu. Rev. Biochem. 63:451–486, 1994.CrossRefPubMedGoogle Scholar
  108. 108.
    Tumlin, J. A., J. P. Lea, C. E. Swanson, C. L. Smith, S. S. Edge, and J. S. Someren. Aldosterone and dexamethasone stimulate calcineurin activity through a transcription-independent mechanism involving steroid receptor-associated heat shock proteins. J. Clin. Invest. 99:1217–1223, 1997.PubMedCrossRefGoogle Scholar
  109. 109.
    Vale, R. D., and R. A. Milligan. The way things move: Looking under the hood of molecular motor proteins. Science 288:88–95, 2000.CrossRefPubMedGoogle Scholar
  110. 110.
    van Kooten, T. G., J. M. Schakenraad, H. C. van der Mei, A. Dekker, C. J. Kirkpatrick, and H. J. Busscher. Fluid shear induced endothelial cell detachment from glass—influence of adhesion time and shear stress. Med. Eng. Phys. 16:506–512, 1994.PubMedGoogle Scholar
  111. 111.
    Wallrabe, U., P. Ruther, T. Schaller, and W. K. Schomburg. Microsystems in medicine. Int. J. Artif. Organs 21:137–146, 1998.PubMedGoogle Scholar
  112. 112.
    Wang, N., J. P. Butler, and D. E. Ingber. Mechanotransduction across the cell surface and through the cytoskeleton. Science 260:1124–1127, 1993.PubMedMathSciNetGoogle Scholar
  113. 113.
    Wang, J. H., P. Goldschmidt-Clermont, J. Wille, and F. C. Yin. Specificity of endothelial cell reorientation in response to cyclic mechanical stretching. J. Biomech. 34:1563–1572, 2001.CrossRefPubMedGoogle Scholar
  114. 114.
    Wang, N., and D. E. Ingber. Control of cytoskeletal mechanics by extracellular matrix, cell shape, and mechanical tension. Biophys. J. 66:2181–2189, 1994.PubMedCrossRefGoogle Scholar
  115. 115.
    Whitesell, L., E. G. Mimnaugh, B. de Costa, C. E. Myers, and L. M. Neckers. Inhibition of heat shock protein hsp90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: Essential role for stress proteins in oncogenic transformation. Proc. Natl. Acad. Sci. U.S.A. 91:8324–8328, 1994.PubMedGoogle Scholar
  116. 116.
    Williams, B. Mechanical influences on vascular smooth muscle cell function. J. Hypertens. 16:1921–1929, 1998.CrossRefPubMedGoogle Scholar
  117. 117.
    Williams, S. E., I. Valenzuela, A. S. Kadish, and K. M. Das. Glomerular immune complex formation and induction of lymphoma in athymic nude mice by tissue filtrates of crohn's disease patients. J. Lab. Clin. Med. 99:827–837, 1982.PubMedGoogle Scholar
  118. 118.
    Wozniak, M., A. Fausto, C. P. Carron, D. M. Meyer, and K. A. Hruska. Mechanically strained cells of the osteoblast lineage organize their extracellular matrix through unique sites of alphavbeta3-integrin expression. J. Bone Miner. Res. 15:1731–1745, 2000.PubMedGoogle Scholar
  119. 119.
    Xu, C. W. High-density cell microarrays for parallel functional determinations. Genome Res. 12:482–486, 2002.PubMedGoogle Scholar
  120. 120.
    Yanagi, S., N. Shimbara, and T. Tamura. Tissue and cell distribution of a mammalian proteasomal atpase, mss1, and its complex formation with the basal transcription factors. Biochem. Biophys. Res. Commun. 279:568–573, 2000.CrossRefPubMedGoogle Scholar
  121. 121.
    Yang, F., and Y. H. Li. Roles of integrins and cytoskeleton in cellular mechanotransduction. Space Med. Med. Eng. (Beijing) 15:309–312, 2002.Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  1. 1.Departments of Mechanical and Biomedical EngineeringCarnegie Mellon UniversityPittsburghUSA
  2. 2.Department of BiologyCollege of the Holy CrossWorcesterUSA
  3. 3.Departments of Mechanical and Biomedical EngineeringCarnegie Mellon UniversityPittsburghUSA

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